Severe selenium deficiency leads to cataract formation in rats. The role of selenium (which is an integral part of glutathione peroxidase), glutathione peroxidase, catalase, and superoxide dismutase in the normal metabolism of the lens and in cataractogenesis will be studied. Severe selenium deficiency will be produced in rats and in acatalasemic mice and the formation of cataract will be followed ophthalmoscopically and by biochemical determinations. These animals will be maintained on selenium deficient diet for several generations and will be challenged with high galactose diet, and an inhibitor of catalase, aminotriazole. Our recent demonstration that catalase bound to red cell membrane exhibits L-DOPA peroxidase activity, will be extended to study the peroxidatic activity in the lens. Two isozymes of glutathione peroxidase are present in the lens. One of the isozymes uses H2O2 and t-butylhydroperoxide, while the other used only t-butylhydroperoxide. In selenium deficiency only the first isozyme is lost. These isozymes will be purified to homogeneity and their selenium content, kinetic and structural properties will be studied. Selenium content of the normal and cataractous human lenses will be determined. Thus, through the completion of these proposed studies, we will have a much better idea of 1) the role of glutathione peroxidase and catalase in the defence mechanism of the lens against oxidants, and 2) the role of selenium in cataractogenesis. Attempts will be made to prevent or delay the sugar cataract formation by manipulating the levels of lens glutathione peroxidase and glutathione reductase and the use of aldose reductase inhibitors. The results may be of great significance in further studies on the prevention of diabetic cataract. In the red cells, three mechanisms of lithium transport are known, 1) a simple diffusion, 2) one that is sensitive to Ouabain and 3) the one that is sensitive to inhibition by Phloretin. Similar studies using rat and mice lens will reinvestigate the mechanism of lithium transport in this tissue.